In humans, skin color arises from a complex series of cellular processes that are carried out within a group of cells known as melanocytes. Melanocytes are located in the lower part of the epidermis and their function is to synthesize a pigment, melanin, which protects the body from the damaging effects of ultraviolet radiation. Melanin is a biopolymer originating from conversions of the amino acids phenylalanine or tyrosine.
The mechanism by which the skin pigment melanin is formed (melanin formation=melanogenesis) and skin ultimately gets its color (skin color=skin pigmentation) is a multi-step process and involves the following main steps:                1) Uptake (active transport via transporter) of amino acid precursors (L-tyrosine, L-phenylalanine) into melanocytes promoted by active transport mechanism        2) Conversion (turnover) of phenylalanine into tyrosine catalyzed by enzyme phenylalanine hydroxylase in melanocytes        3) Uptake (active transport via transporter) of amino acid precursors L-tyrosine into melanosomes located in melanocytes promoted by active transport mechanism        4) Conversion (turnover) of L-tyrosine into L-Dopa by enzyme tyrosinase in melanosome        5) Conversion (turnover) of L-Dopa into dopaquinone by enzyme tyrosinase in melanosome        6) Conversion (turnover) of dopaquinone into two different types of melanin called eumelanin (i.e., darker melanin) and phaeomelanin (i.e., lighter melanin) by various biochemical pathways in melanosome. The amount of each type of melanin determines the color and degree of pigmentation in a person's skin        7) Once melanin is produced, transfer of melanosome with melanin from melanocytes to keratinocytes (which are found in the upper layers of the epidermis) via the melanocyte dendrites.        
In spite of the fact that the chemical and enzymatic basis of melanogenesis and skin pigmentation are rather well-documented, their regulation at the cellular and biochemical level is only partially understood. For instance, it is well known that the activity of tyrosinase is promoted by the action of alpha-melanocyte stimulating hormone (α-MSH) and UV rays. However, the processes of melanosome maturation and melanosome transfer into the keratinocyte are currently far less studied and not yet understood.
Typically, the more melanin is formed, the darker (or more tanned) the skin. However, melanogenesis and skin pigmentation can be disturbed or disorder, which may lead to undesirable pigmentation patterns. Examples of pigmentation disorders (i.e., disorders where pigmentation is disturbed or disordered) include age spots, liver spots, melasma, hyperpigmentation, etc. This has lead to research to find compounds that will inhibit melanogenesis and reduce skin pigmentation. One of the targets of this research is tyrosinase, the enzyme which catalyses the initial steps in the generation of melanin.
Skin pigmentation has been of concern to human beings for many years. In particular, the ability to remove hyperpigmentation (i.e., areas of darker skin color than the surrounding or adjacent, normal pigmented skin), such as found in age spots, freckles or aging skin generally, is of interest to individuals desiring a uniform skin color, skin complexion, or skin tone. In certain areas of the world, general body whitening is desirable.
There are also hypopigmentation (i.e., areas of less dark skin color than the surrounding or adjacent, normal pigmented skin) and hyperpigmentation disorders that are desirable to treat. Likewise, the ability to generate a tanned appearance without incurring photodamage due to solar radiation is important to many individuals.
Many methods proposed to accomplish depigmentation (i.e., reduction or limitation of skin pigmentation or skin color). For example, arbutin, kojic acid, hydroquinone, retinoids, and other chemical compounds have been used for depigmentation. Chemicals that allow depigmentation of skin are also called skin lighteners, skin brighteners, skin whiteners, skin bleachers or actives with skin lightening, skin brightening, skin whitening or skin bleaching properties.
Many of these previous examples were not acceptable or were of limited efficacy in treating skin pigmentation. Most of these compounds have been described to address only a few steps of the multiple steps leading to melanin formation and ultimately skin pigmentation, which may result their limited efficacy. For instance, most chemicals used for depigmentation are described as inhibitors of tyrosinase. Although tyrosinase production and activity is a key factor in melanin formation, melanogenesis is a multi-step process and involves other important and rate-limiting steps than tyrosinase catalyzed conversion of L-tyrosine and L-Dopa and Dopa-quinone. In addition, many of these compounds have been found to be irritating to the skin and, therefore, undesirable for use. Also, precise application of all these compounds may be necessary in order to achieve the desired result and to avoid distinct line of demarcation between the areas of skin to which such previous compositions have been applied.
Accordingly, there is a need for compositions which inhibit melanogenesis and reduce skin pigmentation by modulating one or more of the multiple steps involved in melanogenesis and skin pigmentation. At the same time, there is also a need for compositions that allow skin depigmentation without irritation. The compositions and methods of the present invention address these long felt needs in the art.